novel combinations of cc-122, cc-223, cc-292, and rituximab in diffuse large b-cell lymphoma and follicular lymphoma

Conditions: Lymphoma, Large B-Cell, Diffuse

Summary: first study, at multiple clinical centers, exploring the effects of different combinations of compounds (cc-122, cc-223 ,cc-292 and rituximab) to treat diffuse large b cell lymphoma (dlbcl) and follicular lymphoma

study cc-122-dlbcl-001 is a phase 1b dose escalation and expansion clinical study of cc 122, cc-223 and cc-292 administered orally as doublets with or without rituximab, in participants with relapsed/refractory dlbcl who have failed standard therapy. in expansion phase, selected combination will be administered to lenalidomide naïve fl participants and lenalidomide exposed fl participants in addition to relapsed/refractory dlbcl participants.

Eligibility criteria:
inclusion criteria: * men and women, 18 years or older, with histologically or cytologically-confirmed either: 1. chemo-refractory dlbcl (including transformed low grade lymphoma) 2. lenalidomide naïve; relapsed or refractory cd20-positive follicular lymphoma (grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory fl participants with no prior exposure to lenalidomide (fl-1 cohort) 3. lenalidomide exposed: relapsed or refractory cd20-positive follicular lymphoma (grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (fl-2 cohort), either as a single agent or in combination * at least one site of measurable disease * eastern cooperative oncology group (ecog) performance status (ps) of 0 or 1. * participants must have the following laboratory values: * absolute neutrophil count (anc) ≥ 1.5 x 109/l or ≥ 1.0 x 109/l (with bone marrow involvement with dlbcl) * hemoglobin (hgb) ≥ 8 g/dl. * potassium within normal limits * asparate aminotransferase/serum glutamic oxaloacetic transaminase (ast/sgot) and alanine aminotransferase/serum glutamic-pyruvic transaminase (alt/sgpt) ≤ 2.5 x upper limit of normal (uln) or ≤ 5.0 x uln if liver tumor is present. * serum bilirubin ≤ 1.5 x uln. * estimated serum creatinine clearance of ≥ 50 ml/min * participants must have the following laboratory values: absolute neutrophil count (anc) ≥ 1.5 x 109/l without growth factor support for 7 days (14 days if participants received pegfilgrastim). * males enrolled into treatment arms receiving cc-122 must: agree to abstain from donating sperm while taking ip and for at least 95 days following discontinuation of ip exclusion criteria: * symptomatic central nervous system involvement. * known symptomatic acute or chronic pancreatitis. * persistent diarrhea or malabsorption despite medical management. * peripheral neuropathy ≥ grade 2 * impaired cardiac function or clinically significant cardiac diseases * participants with diabetes on active treatment (for participants treated on cc-223 containing arms only) * prior autologous stem cell transplant (asct) ≤ 3 months before first dose. * prior allogeneic stem cell transplant with either standard or reduced intensity conditioning. * prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting study drugs, whichever is shorter. * participants who have undergone major surgery ≤ 2 weeks prior to starting study drugs. * women who are pregnant or breast feeding. adults of reproductive potential not willing to employ two forms of birth control. * participants with known hiv infection, chronic active hepatitis b or c virus (hbv/hcv) infection. * participants with treatment-related myelodysplastic syndrome. * history of concurrent second cancers requiring active, ongoing systemic treatment. * prior treatment with a dual mtorc1/mtorc2 inhibitor (cc-223 arms only) or btk inhibitor (pci-32765) (cc-292 arms only). \[prior treatment with rapamycin analogues, pi3k or akt inhibitors, lenalidomide and rituximab are allowed\].

Keywords: cc-122 cc-223 cc-292 rituximab lymphoma diffuse large b-cell lymphoma lenalidomide naïve follicular lymphoma lenalidomide exposed follicular lymphoma